CD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemia
<p>CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Frontiers Media
2018
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| _version_ | 1826302721954676736 |
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| author | Marques, LVC Noronha, EP Andrade, FG Dos Santos-Bueno, FV Mansur, MB Terra-Granado, E Pombo-de-Oliveira, MS |
| author_facet | Marques, LVC Noronha, EP Andrade, FG Dos Santos-Bueno, FV Mansur, MB Terra-Granado, E Pombo-de-Oliveira, MS |
| author_sort | Marques, LVC |
| collection | OXFORD |
| description | <p>CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in <em>N/KRAS, NOTCH1, FBXW7</em> as well as <em>STIL-TAL1</em> and <em>TLX3</em> rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1–1272), T-ALL was relatively low, with MFI 43.2 (1.9–1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1a<sup>neg</sup>) had a lower CD44 expression, MFI 57.5 (2.7–866.3), whereas mCD3/TCRγδ<sup>pos</sup> cases had higher expressions, MFI 99.9 (16.4–866.3). <em>NOTCH1</em><sup>mut</sup> and <em>STIL-TAL1</em> were associated with low CD44 expression, whereas <em>N/KRAS</em><sup>mut</sup> and <em>FBXW7</em><sup>mut</sup> cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (<em>p</em> = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL.</p> |
| first_indexed | 2024-03-07T05:51:52Z |
| format | Journal article |
| id | oxford-uuid:e92804f8-fc8b-45b1-901b-53a4dfcf06b8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:51:52Z |
| publishDate | 2018 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:e92804f8-fc8b-45b1-901b-53a4dfcf06b82022-03-27T10:52:14ZCD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e92804f8-fc8b-45b1-901b-53a4dfcf06b8EnglishSymplectic ElementsFrontiers Media2018Marques, LVCNoronha, EPAndrade, FGDos Santos-Bueno, FVMansur, MBTerra-Granado, EPombo-de-Oliveira, MS<p>CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in <em>N/KRAS, NOTCH1, FBXW7</em> as well as <em>STIL-TAL1</em> and <em>TLX3</em> rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1–1272), T-ALL was relatively low, with MFI 43.2 (1.9–1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1a<sup>neg</sup>) had a lower CD44 expression, MFI 57.5 (2.7–866.3), whereas mCD3/TCRγδ<sup>pos</sup> cases had higher expressions, MFI 99.9 (16.4–866.3). <em>NOTCH1</em><sup>mut</sup> and <em>STIL-TAL1</em> were associated with low CD44 expression, whereas <em>N/KRAS</em><sup>mut</sup> and <em>FBXW7</em><sup>mut</sup> cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (<em>p</em> = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL.</p> |
| spellingShingle | Marques, LVC Noronha, EP Andrade, FG Dos Santos-Bueno, FV Mansur, MB Terra-Granado, E Pombo-de-Oliveira, MS CD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemia |
| title | CD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemia |
| title_full | CD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemia |
| title_fullStr | CD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemia |
| title_full_unstemmed | CD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemia |
| title_short | CD44 expression profile varies according to maturational subtypes and molecular profiles of pediatric T-cell lymphoblastic leukemia |
| title_sort | cd44 expression profile varies according to maturational subtypes and molecular profiles of pediatric t cell lymphoblastic leukemia |
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